title: FAST-Mag protocol with or without mild hypothermia (35°C) does not improve outcome after permanent MCAO in rats.
abstract: The current study assessed the neuroprotective efficacy of magnesium using a FAST-Mag trial treatment protocol alone, and in combination with mild hypothermia, in Sprague Dawley rats subjected to permanent, middle cerebral artery occlusion (MCAO). Treatment with magnesium (MgSO4.7H2O) consisted of an intravenous loading dose (LD: 360 μmol/kg) and a 24 hour infusion (120 μmol/kg/h), while mild hypothermia at 35°C was maintained for 24 hours. Treatment groups consisted of animals receiving: i) saline; ii) magnesium LD/infusion at 1.5 h/2.5 h post-MCAO; iii) magnesium LD/infusion at 1.5 h/2.5 h post-MCAO and hypothermia commencing at 2.5 h post-MCAO; iv) magnesium LD and hypothermia at 1.5 h and magnesium infusion at 2.5 h post-MCAO; v) hypothermia commencing at 1.5 h post-MCAO and magnesium LD/infusion at 2.5 h post-MCAO; and vi/vii) hypothermia commencing at 1.5 h or 2.5 h post-MCAO. No treatment significantly reduced infarct volumes or improved adhesive tape removal time when measured 48 hours after MCAO. These findings indicate that FAST-Mag treatment alone or with mild hypothermia may not provide benefit after ischemic stroke, associated with permanent cerebral artery occlusion.
authors.affiliation: Centre for Neuromuscular and Neurological Disorders/University of Western Australia, Australian Neuro-Muscular Research Institute and Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. bruno.meloni@anri.uwa.edu.au
authors.forename: Bruno P
authors.initials: BP
authors.lastname: Meloni
authors.forename: Jane L
authors.initials: JL
authors.lastname: Cross
authors.forename: Laura M
authors.initials: LM
authors.lastname: Brookes
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Clark
authors.forename: Kym
authors.initials: K
authors.lastname: Campbell
authors.forename: Neville W
authors.initials: NW
authors.lastname: Knuckey
mesh_terms: D000818:Animals; D001831:Body Temperature; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology; D007036:Hypothermia, Induced; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology; D008274:Magnesium / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
chemical_list: D008274:Magnesium
keywords: FAST-Mag; MCAO; Sprague Dawley rats; magnesium; mild hypothermia; stroke